Coronavirus, the King Who Wanted More Than a Crown: From Common to the Highly Pathogenic SARS-CoV-2, Is the Key in the Accessory Genes?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that emerged in late 2019, is the etiologic agent of the current “coronavirus disease 2019” (COVID-19) pandemic, which has serious health implications and a significant global economic impact. Of the seven human coronaviruses, all of which have a zoonotic origin, the pandemic SARS-CoV-2, is the third emerging coronavirus, in the 21st century, highly pathogenic to the human population. Previous human coronavirus outbreaks (SARS-CoV-1 and MERS-CoV) have already provided several valuable information on some of the common molecular and cellular mechanisms of coronavirus infections as well as their origin. However, to meet the new challenge caused by the SARS-CoV-2, a detailed understanding of the biological specificities, as well as knowledge of the origin are crucial to provide information on viral pathogenicity, transmission and epidemiology, and to enable strategies for therapeutic interventions and drug discovery. Therefore, in this review, we summarize the current advances in SARS-CoV-2 knowledges, in light of pre-existing information of other recently emerging coronaviruses. We depict the specificity of the immune response of wild bats and discuss current knowledge of the genetic diversity of bat-hosted coronaviruses that promotes viral genome expansion (accessory gene acquisition). In addition, we describe the basic virology of coronaviruses with a special focus SARS-CoV-2. Finally, we highlight, in detail, the current knowledge of genes and accessory proteins which we postulate to be the major keys to promote virus adaptation to specific hosts (bat and human), to contribute to the suppression of immune responses, as well as to pathogenicity.

MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells

“…One example of homologous proteins in two different betacoronavirus lineages is the PDEs of merbecoviruses (NS2) and embecoviruses (NS4b); however, these proteins differ in that only NS4b contains an NLS and has a second function in host antagonism ( 21 , 22 , 28 – 31 , 50 ). The SARS-CoV-2 genome encodes sarbecovirus lineage-specific accessory proteins encoded in ORF3a, ORF3b, ORF6, ORF7a, and ORF9b, which have all been reported to be IFN antagonists ( 51 , 52 ). Most notably, the ORF6 encoded protein of SARS-CoV and SARS-CoV-2 blocks STAT1/STAT2 translocation into the nucleus, thus impairing induction of ISGs ( 53 , 54 ).…”

Inhibitors of SARS-CoV-2 PLpro

“…Assembly of new viral particles and exocytosis of the mature virions through the formation of double membraned vesicles (DMVs) completes the viral life cycle ( Hartenian et al, 2020 ; V’kovski et al, 2020 ). The roles of each of the viral structural/accessory protein and non-structural proteins (nsps) have been studied extensively ( Hartenian et al, 2020 ; V’kovski et al, 2020 ; Chazal, 2021 ). Targeting essential steps early in the process of viral replication has been the most successful strategy to stop CoV infection.…”

Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation

“…In the last two decades, three novel Betacoronaviruses have entered human circulation from zoonotic sources and caused infections with high morbidity and mortality. This group includes the severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV2 virus that appeared in late 2019 and caused the most devastating respiratory virus pandemic since the 1918 Spanish Flu (2)(3)(4)(5). The relatively genomes of Betacoronaviruses are ~30 kb and encode 4-5 structural proteins and 16 nonstructural proteins (Nsp1-16) (1,(6)(7)(8).…”